Identification of Positive Valence System Related Targets for Novel Suicide Prevention Approaches (R01 - Clinical Trial Optional) | PAS 21 216

Opportunity Information: Apply for PAS 21 216

The NIH funding opportunity "Identification of Positive Valence System Related Targets for Novel Suicide Prevention Approaches (R01 - Clinical Trial Optional)" (PAS-21-216) supports research projects that focus on how positive affect (PA) and related reward-based processes function in people at elevated risk for suicide, and how those processes can be measured and changed in ways that could inform new prevention strategies. The central idea is that suicide risk research often emphasizes negative emotion, distress, and threat, but this FOA pushes investigators to dig into the "positive valence system" side of the picture: reward responsiveness, anticipation of positive outcomes, pleasure, motivation, learning from rewarding experiences, and related cognitive and emotional mechanisms that may be blunted, unstable, or otherwise disrupted in suicidal states.

Projects are expected to include clinical populations with high suicide risk, such as individuals who have attempted suicide or who are currently acutely suicidal. Studies can also include comparison groups where useful, including non-suicidal patients, people considered high risk even without a formal diagnosis, and healthy controls. NIH explicitly welcomes work spanning the full developmental spectrum, so proposals may target adolescents, adults, older adults, or multiple age groups, as long as the project clearly ties developmental considerations to positive affect/reward mechanisms and suicide risk.

Scientifically, the FOA encourages applicants to do three main things. First, a project should clearly specify the construct it aims to study. This can be framed using the NIMH Research Domain Criteria (RDoC) Positive Valence Systems (PVS) framework, or using a closely related symptom-relevant construct. Examples named in the announcement include anhedonia (including potential subtypes), reward-based decision making in the present versus the future, and the ability to generate "reasons for living" tied to anticipating positive experiences. The key is not just naming a broad concept like "reward," but defining a specific, testable construct that can be operationalized with behavioral, self-report, computational, and/or neurobiological measures.

Second, applicants are encouraged to show that their measures of the construct are reliable and reproducible and that they map onto brain subsystems relevant to positive affect and reward processing. In practice, this means proposals should make a strong case that their tasks, metrics, or biomarkers are stable enough to be trusted, can be replicated, and meaningfully engage neural circuitry implicated in positive valence functions. While the FOA does not prescribe a specific method, the language points toward work that bridges behavior with neural measures (for example, fMRI, EEG/ERP, psychophysiology, or other neuroscience approaches) in a way that strengthens mechanistic interpretation.

Third, the FOA encourages projects that go beyond observation and actually test whether the targeted positive valence construct and its underlying circuitry can be modified. This includes studies using behavioral training, as well as "therapeutic probes" such as non-invasive neuromodulation, pharmacological approaches, or psychosocial interventions, with outcomes that include both behavioral measures of the construct and indicators of brain system engagement or change. Importantly, the mechanism matters here: the goal is not simply to reduce symptoms in general, but to demonstrate active modification of a specific positive valence-related target that is plausibly tied to suicide risk.

In terms of experimental approaches, the FOA allows both novel and established behavioral tasks within the RDoC positive valence domain. Examples highlighted include reward sensitivity, reward valuation, and reward learning, as well as tasks that probe components of hedonic experience and related subconstructs. A notable emphasis is placed on measuring dynamic changes in positive affect, rather than relying only on static, one-time assessments. NIH "strongly encourages" capturing how PA fluctuates over time, which can help clarify how shifts in positive emotion co-occur with other risk factors and with suicidal thinking or behavior. This points to designs that might include repeated assessments, intensive longitudinal methods, or other approaches suited to tracking within-person change.

Administratively, this is an R01 mechanism with "clinical trial optional," meaning applicants may propose either clinical trial or non-clinical trial research, depending on the design and whether an intervention is being tested in a way that meets the NIH clinical trial definition. The sponsoring agency is the National Institutes of Health, the activity category is health (CFDA 93.242), and the funding instrument is a grant under a discretionary opportunity category. While the listing provided does not specify an award ceiling or expected number of awards, the intent is clearly to fund substantial, hypothesis-driven projects consistent with the scope of an R01.

Eligibility is broad and includes many types of U.S. organizations and governmental entities: state, county, and city/township governments; special districts; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; small businesses; for-profit organizations (other than small businesses); federally recognized Native American tribal governments and other tribal organizations; public housing authorities and Indian housing authorities; and nonprofits both with and without 501(c)(3) status. The FOA also explicitly calls out additional eligible applicant categories, including Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving Institutions, Historically Black Colleges and Universities, Tribally Controlled Colleges and Universities, eligible federal agencies, faith-based and community-based organizations, regional organizations, U.S. territories or possessions, and non-U.S. entities (foreign organizations). The opportunity was created on 2021-04-16, with an original closing date listed as 2021-10-05.

Overall, the grant is aimed at advancing suicide prevention by identifying and validating actionable targets tied to positive affect and reward functioning, grounding those targets in reliable measurement and relevant neural systems, and testing whether they can be changed through well-justified experimental or intervention approaches in populations where suicide risk is clinically meaningful.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Identification of Positive Valence System Related Targets for Novel Suicide Prevention Approaches (R01 - Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.242.
• This funding opportunity was created on 2021-04-16.
• Applicants must submit their applications by 2021-10-05. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

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